Dialysis is one of the most commonly known and used extracorporeal blood treatment methods and is intended to replace the function of the kidneys when a renal failure of the kidneys occurred in a patient.
When the kidneys fail, dialyzing a patient is necessary to remove waste products such as urea, creatinine and uremic toxins from the blood of the patient. Furthermore, during dialysis, excess water and other substances which are usually eliminated by urine are removed from the body of the patient. The most commonly used method of dialysis is hemodialysis in which the blood of the patient flows along a dialyzing membrane, wherein on the other side of this dialyzing membrane a dialyzing liquid is provided. Accordingly, blood and dialyzing liquid are separated by the porous membrane.
Through this membrane, the substances which are to be removed from the blood of the patient diffuse because of a concentration gradient between blood and the dialyzing liquid. Larger molecules, whose diffusion velocity is very slow, can also be transported convectively by means of a liquid flow from the blood side to the dialysis liquid side of the membrane.
The dialysis liquid is prepared to have a concentration which provides for a concentration gradient from the blood side to the dialysis liquid side for certain substances, but not necessarily for all substances. In fact, the removal of urea and creatinine as well as other waste products in the human body is desired but, for example, the removal or change of concentration of electrolytes such as potassium, sodium or bicarbonate is not at all desired but is considered harmful. Accordingly, the dialysis liquid typically contains a concentration of the electrolytes which resembles the concentration of electrolytes in the blood plasma of the patient such that a concentration gradient is not present for these substances.
Besides the hemodialysis, peritoneal dialysis is another dialysis method which also uses a membrane and a dialysis liquid in order to achieve a diffusion of the waste product through the membrane into the dialysis liquid. The membrane, however, is a natural membrane namely the peritoneum and the dialysis liquid is introduced directly into the abdominal cavity.
During dialysis, the elimination of excess water and small molecular uremic substances such as urea and creatinine is typically no problem, larger molecules, however, are more difficult to remove through the porous membrane. In order to tackle this, specific high flux dialysis membranes are provided in combination with highly convective methods, such as hemodiafiltration. This results in improvements in the clearance of molecules of molecular masses over 1 kDa, which is the range of the so-called middle-sized molecules. In hemodiafiltration, a diffusion method using the dialysis liquid in the form as described above is combined with hemofiltration, in which the blood of a patient is subjected to a pressure gradient across a filter. Accordingly, the filtration process along the pressure gradient leads to an increased liquid flow and is, thus, considered a highly convective method which enables the removal of a considerable portion of middle-sized molecules. However, due to the pressure gradient, water as well as electrolytes and sugars are also removed from the blood of the patient at a high rate such that these blood constituents have to be replaced by means of the infusion of a replacement fluid.
The introduction of the high flux dialysis membranes in combination with highly convective methods improves the clearance for middle-sized and larger molecules.
Larger molecules are typically proteins, wherein, for example, beta2-microglobulin has a size of about 11 kDa, wherein this molecule may induce an amyloidosis if not sufficiently removed. Smaller molecules which are toxic may also be difficult to dialyze if the molecules are bound to proteins. For example, uremic toxins which are bound to proteins are p-cresyl sulfate and indoxyl sulfate.
Accordingly, it is desired to have pore sizes in the dialysis membranes which are sufficiently large to let through these middle-sized molecules. On the other hand, the pore size of the membrane cannot be extended infinitely, because the higher the pore size of the membrane, the higher the risk that vital blood components are likewise lost. Accordingly, the permeability of the membrane is typically limited to sizes of around 60 kDa. However, this value is just slightly below the molecular mass of human plasma albumin which has a size of about 66 kDa. In practice, clinically significant losses of albumin may happen wherein these losses significantly depend on the respective parameters of the method, such as the respective pressures and the respective concentrations in the dialysis liquid. In particular, a high flux membrane in combination with the pressure gradient applied during hemofiltration increases the clearance of human albumin. Another reason for the loss of human albumin may be the multiple use of the membranes because the cleaning of the membrane which is necessary between different treatments tends to increase the sizes of the pores in the membrane. This shifts the permeability of the membrane towards higher molecules. Accordingly, even under normal conditions in normal hemodialysis, human serum albumin may penetrate through the membrane.
It goes without saying that in the case of the peritoneal dialysis the sizes of the pores of the membrane cannot be influenced but are given by the condition of the peritoneum of the respective patient. However, a loss of human albumin into the dialysis liquid may nevertheless take place once the peritoneum has been impaired, for example, by an inflammation.
In order to determine the clearance of an analyte during dialysis, a Raman spectroscopy method is disclosed in US 2008/0158544 A1, wherein the Raman spectral measurements are carried out on the blood after it has passed the dialyzer in order to utilize the unique Raman spectroscopic signature of one or more analytes, e.g., urea, to identify and quantify such analytes against a whole blood background.
WO 2010/091826 A1 relates to an apparatus for the extracorporeal treatment of blood, wherein the absorption of electromagnetic radiation in the dialysis liquid is measured in order to determine the Kt/V value, namely the clearance K of the volume flow of the clean substances, wherein t is the treatment time and V the distribution volume of the patient. In renal replacement therapy, urea is typically used as a marker substance for measuring treatment efficiency of uric acid, such that K is the uric acid clearance and V the urea distribution volume of the patient, which corresponds, in principle, to the body water of the patient. However, by measuring the total absorption, in general the clearance for a specific molecule cannot be determined.
Accordingly, it is desired to monitor the loss of human albumin during dialysis treatments in order to alert the medical personnel of this condition, such that the treatment can be adjusted or even to automatically adjust or even interrupt the treatment in case of excessive loss of albumin.
Furthermore, other proteins such as the above-mentioned middle molecules (proteins with sizes of smaller than 66 kDa) as well as further smaller molecular substances such as p-cresyl sulfate, indoxyl sulfate or phenyl are also to be determined as to their clearance because these substances are toxic.